Despite recent declines in both mortality and incidence, colorectal cancer is currently the third most common cancer diagnosed and the third leading cause of cancer death in the United States for both men and women. It is not known to what extent this decline is attributable to changes in use of screening, changes in exposures to "lifestyle" risk and protective factors, changes in treatment, or combinations of these factors. Theoretically more than 50% of colorectalcancer could be prevented by modification in screening, lifestyle, and chemoprevention practices. Mathematical modeling of the colorectal cancer incidence and mortality rates over time can estimate the separate and joint effects of screening, lifestyle changes, and changes in treatment for different subgroups of the population. The Department of Public Health, Erasmus University Rotterdam, has developed a comprehensive micro-simulation model of the adenoma-carcinoma sequence for colorectal cancer (MISCAN) which has been used to assess the potential effects of screening interventions and can incorporate varying risk groups in its description and outcomes. This model simulates a full dynamic population which makes it particularly suitable for surveillance of population trends. We will refine this model further to include more flexibility for risk strata and to incorporate the advanced adenoma as the intermediate marker for colorectal cancer risk, and to allow for differential survival post-diagnosis based on treatment. The key question we plan to address concerns the impact of colorectal cancer screening on mortality trends. The specific aims of this study are to 1) update and refine the MISCAN model with best estimates of risk factors, screening, and treatment practices; 2) use the MISCAN microsimulation model to estimate the absolute and relative contribution of colorectal cancer screening, risk factors, and improved therapy on observed colorectal cancer incidence and mortality trends; 3) use the MISCAN model to predict how changes in colorectal cancer screening and treatment practices will affect future incidence and mortality. This study will provide an understanding of the absolute and relative contribution of screening, lifestyle factors, and improved therapy on incidence and mortality trends. This is essential for directing medical and public health resources to the most effective interventions in the appropriate risk groups.